Prior Auth Protocol

FDA Approved Indications:

For the treatment of genotype 1 or 4 chronic hepatitis C virus (HCV) infection with or without ribavirin in adults

Health Net Approved Indications and Usage Guidelines:

Diagnosis of chronic hepatitis C (CHC) confirmed by detectable serum HCV RNA by quantitative assay in patients with genotype 1 or 4. Genotype is required to determine length of approval.

AND

For genotype 1a, laboratory testing for the presence or absence of virus with NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31, or 93 [See General Information section]

AND

Patient is 18 years of age or older

AND

Any of the following clinical states identify candidates for treatment:
- Evidence of Stage 2 or greater hepatic fibrosis including one of the following: Liver biopsy confirming a METAVIR score F2 or greater OR Transient elastography (Fibroscan.), score greater than or equal to 7.5 kPa; OR FibroSure. (also known as FibroTest) score of greater than or equal to 0.48; OR APRI score greater than 0.7; OR FIB greater than 3.25.
- Evidence of extra-hepatic manifestation of hepatitis C virus, such as type 2 or 3 essential mixed cryoglobulinemia with end- organ manifestations (e.g. vasculitis), or kidney disease (e.g. proteinuria, nephrotic syndrome or membranoproliferative glomerulonephritis).
- Persons with hepatocellular carcinoma with life expectancy greater than 12 months
- Pre- and post-liver transplant, or other solid organ transplant
- HIV-1 co-infection
- Hepatitis B co-infection
- Other coexistent liver disease (e.g. nonalcoholic steatohepatitis)
- Type 2 diabetes mellitus (insulin resistant)
- Porphyria cutanea tarda
- Debilitating fatigue impacting quality of life (e.g., secondary to extra-hepatic manifestations and/or liver disease)
- Men who have sex with men with high-risk sexual practices
- Active injection drug users
- Persons on long-term hemodialysis
- Women of childbearing age who wish to get pregnant
- HCV-infected health care workers who perform exposure-prone procedures

Criteria for Reauthorization/Continuation of Therapy:

Initial authorization criteria have been met, and
Evidence of lack of adherence may result in denial of treatment reauthorization.
Missed medical appointments related to the hepatitis C virus may result in denial of treatment authorization.

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

For patients infected with HCV Genotype 1a: Testing for the presence of virus with NS5A resistance-associated polymorphisms is recommended. Clinical trial results show decreased efficacy of Zepatier in HCV genotype 1a with presence of NS5A polymorphisms. If baseline NS5A polymorphisms are presentfor genotype 1a, refer to Section VI on the longer recommended duration of therapy.
Zepatier is contraindicated with organic anion transporting polypeptides 1B1/3 (OATP1B1/3)
inhibitors, strong inducers of cytochrome P450 3A (CYP3A), and efavirenz.
Zepatier is contraindicated for use in patients with moderate to severe hepatic impairment (Child-Pugh Class B or Class C) due to the expected significantly increased grazoprevir plasma concentration and the increased risk of alanine aminotransferase (ALT) elevations.
Child-Pugh Score:

	1 Point	2 Points	3 Points
Bilirubin	Less than 2 mg/dL Less than 34 umol/L	2-3 mg/dL 34-50 umol/L	Over 3 mg/dL Over 50 umol/L
Albumin	Over 3.5 g/dL Over 35 g/L	2.8-3.5 g/dL 28-35 g/L	Less than 2.8 g/dL Less than 28 g/L
INR	Less than 1.7	1.7 - 2.2	Over 2.2
Ascites	None	Mild / medically controlled	Moderate-severe / poorly controlled
Encephalopathy	None	Mild / medically controlled Grade 1-11	Moderate-severe / poorly controlled. Grade III-IV

Diagnostic criteria for chronic fatigue syndrome was developed by an expert committee convened by the Institute of Medicine on the basis of a comprehensive literature review and input from patient, advocacy, and research communities. These diagnostic criteria state that symptoms should persist for at least 6 months and be present at least half the time with moderate, substantial, or severe intensity to distinguish chronic fatigue syndrome from other diseases.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
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* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Zepatier	Genotype 1a: Treatment-naive or PegIFN/RBV experienced without baseline NS5A polymorphisms at amino acid positions 28, 30, 31, or 93 One tablet PO QD	12 weeks
Zepatier	Genotype 1b: Treatment-naive or PegIFN/RBV experienced One tablet PO QD	12 weeks
Zepatier	Genotype 4: Treatment-naive One tablet PO QD	12 weeks
Zepatier + ribavirin	Genotype 1a: Treatment-naive or PegIFN/RBVexperienced with baseline NS5A polymorphisms at amino acid positions 28, 30, 31, or 93 One tablet PO QD plus BID ribavirin	16 weeks
Zepatier + ribavirin	Genotype 1a or 1b: PegIFN/RBV/PI-experienced One tablet PO QD plus BID ribavirin	12 weeks
Zepatier + ribavirin	Genotype 4: PegIFN/RBV-experienced One tablet PO QD plus BID ribavirin	16 weeks

Product Availability:

Zepatier Tablets: grazoprevir 100 mg/elbasvir 50 mg

References:

1. Zepatier [Prescribing Information]. Whitehouse Station, NJ: Merck and Co.; January 2016.
2. Zeuzem SJ, Ghalib R, Reddy R, et al. Grazoprevir-elbasvir combination therapy for treatment naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4 or 6 infection. Annals of Int Med July 7, 2015;163;1:1-13.
3. American Association for the Study of Liver Disease Recommendations for Testing, Managing, and Treating Hepatitis C; December 2015. (accessed at: http://www.hcvguidelines.org).